From Club to Clinic: The Treatment of PTSD with MDMA

Written By Erin Kaufman

Erin Kaufman

Illustrations by Iris Li

Difficult experiences are universal. However, in extreme cases, past traumas can resurface, interrupting daily life. Post traumatic stress disorder, or PTSD, is a psychiatric disorder that can lead to a variety of emotional and physical symptoms in response to a singular or repeated extreme traumatic event [1, 2]. While not everyone who experiences a traumatic event will develop PTSD, those who do may not present with the disorder in the same way and may respond to treatment differently [3, 4]. Due to the individuality of PTSD diagnoses, there is not one specific treatment plan to alleviate PTSD symptoms [5, 6]. While current medication paired with therapy may relieve symptoms for some, just under half of people diagnosed with PTSD experience treatment resistance [7]. In response to the prevalence of treatment-resistant PTSD, investigations have begun into new methods of treatment, particularly in first responders and military personnel [8]. MDMA, more commonly known as ecstasy, is a promising option for an alternative treatment avenue [9, 10].

Systems and Symptoms: PTSD and its Treatments

PTSD is often associated with a persistent negative emotional state and feelings of anxiety and depression, but because of the case-specific nature of the diagnosis, the range of symptoms will vary [1, 5, 6, 11]. Diagnostic criteria also include intrusive and disturbing memories, flashbacks, and physiological reactions, such as a rapid heartbeat, dizziness, and insomnia [1, 11]. An individual diagnosed with PTSD will likely express two main kinds of symptoms [1, 2]. These two types are categorized as hyperarousal symptoms — anxiety, hypervigilance, re-experiencing the traumatic event — and avoidance symptoms — withdrawal and emotional numbness [1, 2]. These symptoms can lead to months or even years of suffering [2].

PTSD develops through the disruption of fear memory systems in the brain [12]. Given the duration and repetitive nature of PTSD, exploring its connections to both fear and memory is essential to battling people’s physiological and psychological symptoms [2, 13]. Fear is encoded in neurological circuits of a brain structure called the amygdala, which is intricately involved in emotional processing and is the master coordinator of fear memory [14, 15, 16]. Dopamine and serotonin are neurotransmitters, or signaling molecules, that help create strong fear memories when released in the amygdala [17, 18]. Although fear memory allows people to differentiate between what is harmful and what is safe, dysregulation of this system can lead to the maladaptive responses seen in PTSD [12, 19].

People with PTSD currently have only two medication options available to help combat emotional duress and resulting maladaptive responses, both of which alter serotonin activity in the brain [20, 21]. Serotonin is a versatile neurotransmitter that regulates systems such as those for mood and sleep [22]. A process called reuptake halts serotonin signaling by bringing serotonin molecules out of the synapse — the space between brain cells — and back into the cell [23]. The medications for PTSD treatment are selective serotonin reuptake inhibitors (SSRIs), which act by preventing reuptake, therefore keeping serotonin in the synapse and prolonging its effects [24]. SSRIs paired with psychotherapy can help reduce the frequency and severity of symptoms for some people with PTSD [13, 25, 26]. However, this combined treatment is not effective for every person; over one-third of people suffering from PTSD fail to see improvement in their symptoms with prescribed SSRIs and psychotherapy [13, 25, 26].

The Ecstatic Brain: Neural Effects of MDMA

In response to the prevalence of treatment-resistant PTSD, an alternative substance has become the focus of treatment studies: MDMA [20, 26]. MDMA is a widely used illicit substance in the U.S. [27]. It has both hallucinogenic and stimulant properties, giving people who use it a combination of dissociative, out-of-body feelings and increased mental alertness and energy [9]. The combination of these effects in MDMA goes beyond improving the internal experience of the user; the drug has unique prosocial behavioral effects, such as increased sociability and enhanced feelings of trust, openness, and closeness with others [28, 29]. Therefore, MDMA has been considered as a new method of treatment for patients with PTSD as it can help them better process their trauma during talk therapy [4, 7, 9, 10, 13, 30].

Another reason MDMA-assisted therapy has been explored as an alternative PTSD treatment is because of its effect on dopamine and serotonin pathways, particularly in the amygdala [4, 13, 31]. Like SSRIs, MDMA reduces serotonin reuptake, but it also has a secondary effect on dopamine reuptake [28, 32]. MDMA affects serotonin and dopamine packaging before the neurotransmitters leave the cell, allowing them to be packed and released in higher quantities [28, 32]. When dopamine levels are increased people report an increase in awareness and motivation to engage in psychotherapy [9, 25]. Increased serotonin and dopamine levels contribute to increased self-confidence, reduced amygdala fear response, and greater compassion and empathy for oneself and others [25].

MDMA also has unique effects on the brain because it is thought to promote the release of oxytocin [1, 33]. Oxytocin is a molecule often associated with love and social bonding, and it is involved in feelings of safety, sociability, and sexual arousal [34]. For instance, hugging a friend or loved one can increase oxytocin levels [35]. Beyond its prosocial effects, oxytocin can help people cope with stress while navigating traumatic situations [34, 35]. When an individual is under the influence of MDMA, their increased sociability is theorized to be related to an excessive release of oxytocin [33, 36, 37]. High oxytocin levels can increase awareness of both positive and negative social experiences [33]. On the other hand, MDMA increases awareness of positive social experiences and limits awareness of negative social experiences [33]. While the prosocial effects of MDMA may be related to oxytocin levels, it is the complexity of the drug’s neurochemical effects that causes a beneficial prosocial experience in therapy [37, 38, 39].

MDMA use also significantly affects the hippocampus, a brain structure primarily involved in memory retention, reactivation, and reconsolidation [30, 40]. The hippocampus contributes to the memory component of the fear memory circuits that also route through the amygdala [30, 40, 41, 42, 43]. During memory reconsolidation, memories are reaccessed, reformed, and stored differently than before [42, 44, 45]. When a person revisits the memory of a traumatic event in therapy they are able to think about it in a new way, forming a less emotionally volatile version of that memory [40]. MDMA affects hippocampal activity in fear memory circuits, potentially allowing a person to reform the traumatic memory with less emotional weight [30, 40]. Therefore, people in therapy under the influence of MDMA are able to discuss their traumatic memories with fewer physiological and psychological pains [13].

Although MDMA can be beneficial in a clinical setting, cell death that results from the abuse of MDMA can cause damage to major memory circuits [30, 46]. MDMA abuse can cause damage to overactive serotonin receptors in the brain and serotonin-sensitive nerve endings in the hippocampus [43]. This potential danger seen in chronic use has led to the neglect of MDMA as a potential therapeutic [30]. Consequently, MDMA is legally classified as a Schedule 1 drug: a drug with no current accepted medical use in the United States and a high potential for abuse [47]. However, a controlled dosage of MDMA taken in a medical setting is significantly less likely to cause permanent damage to the brain and has a variety of possible benefits [4]. MDMA-assisted therapy is now in the process of getting approved by the Food and Drug Administration (FDA) for medicinal use [48]. If FDA approved, MDMA would no longer be considered a Schedule 1 drug and could be implemented for treatment in controlled environments [47].

Unlocking the Gate: MDMA’s Role in Clinical Treatment

Think of PTSD as a locked gate, with the recollection of traumatic memories lying behind that gate. By providing access to those memories in the brain in a way that does not physically or emotionally harm someone, MDMA acts as a key to making people more emotionally and cognitively receptive toward treatment [7, 13]. During a therapy session, a person receives a controlled dosage of MDMA in a supervised clinical setting and meets with psychiatrists and psychologists to access the traumatic memory [4, 7, 10, 23]. The doctors help those receiving treatment recount memories that would normally trigger severe PTSD symptoms while ensuring that they feel safe under the influence of MDMA. As MDMA can inhibit fear systems in the amygdala and provide people with a heightened sense of self-awareness, doctors can probe traumatic memories without triggering the person receiving treatment [7, 13]. MDMA alone is not known to treat any neurological disorder, but it can provide people with a greater sense of trust and security to process distressing events during psychotherapy [7, 13].

Due to long-term exposure to military combat, terrorism, violent crime, and death, military veterans are especially likely to be diagnosed with PTSD [4]. Veterans can receive MDMA-assisted therapy to treat these wounds and provide a sense of emotional and social comfort, allowing them to speak about their trauma without experiencing PTSD symptoms [4, 7, 10, 13]. During MDMA-assisted therapy, memory reconsolidation can help people address their PTSD and trauma responses [47]. When veterans suffering from PTSD are able to speak about traumatic events in a secure setting under the prosocial and mood-boosting effects of MDMA, they can reconsolidate their memory of traumas into memories that do not provoke the same PTSD symptoms [7, 13]. In a recent phase three clinical trial for MDMA-assisted therapy as a treatment for PTSD, about two-thirds of veterans participating in the trial no longer met the eligibility criteria for PTSD after three sessions of MDMA therapy, compared to less than half of veterans who did not receive MDMA [4]. Although there is individual variability in the reactions to and efficacy of MDMA-assisted therapy for PTSD, the overall potential of MDMA treatment offers the exciting prospect of a safe and effective treatment plan [4, 7, 10, 13].

While the first studies of MDMA-assisted therapy focused on PTSD treatment for military veterans and first responders, more recent studies show that MDMA-assisted therapy has been effective in people who have experienced vastly different traumas [7, 13]. For example, historically underrepresented populations in PTSD clinical trials — including survivors of chronic sexual violence, transgender individuals, and ethnoracial minorities — have been shown to experience an alleviation of PTSD symptoms after MDMA-assisted therapy [13]. Despite the uniqueness of each diagnosis, MDMA-assisted therapy is beginning to open the door to reliable treatment for people from a broad range of backgrounds who are living with PTSD [4, 7, 10, 13].

A Shift in Culture: the Rise of Alternative Treatments

MDMA-related treatment results for PTSD have only come to light in recent years [8]. Due to the stigma against substances and the anti-drug movements of the 1970s, avenues for MDMA treatment have been prohibited and ignored [49]. However, as cultural perspectives on drugs have shifted over the years, new perspectives have suggested MDMA and its benefits as a potential treatment for PTSD [21, 25]. For the first time since the 1960s, the government is funding research on MDMA for treatment of PTSD in military veterans and first responders [20, 50]. In December 2023, MDMA-assisted therapy was brought to the FDA to obtain approval for medicinal use outside of clinical studies [47]. If approved, MDMA could become an alternative treatment to SSRIs and give people with PTSD a chance to live without the constraints of their past traumas [50].

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Erin Kaufman
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